A pan-cancer screen identifies drug combination benefit in cancer cell lines at the individual and population level.

ABSTRACT: Combining drugs can enhance their clinical efficacy, but the number of possible combinations and inter-tumor heterogeneity make identifying effective combinations challenging, while existing approaches often overlook clinically relevant activity. We screen one of the largest cell line panels (N = 757) with 51 clinically relevant combinations and identify responses at the level of individual cell lines and tissue populations. We establish three response classes to model cellular effects beyond monotherapy: synergy, Bliss additivity, and independent drug action (IDA). Synergy is rare (11% of responses) and frequently efficacious (>50% viability reduction), whereas Bliss and IDA are more frequent but less frequently efficacious. We introduce "efficacious combination benefit" (ECB) to describe

SUBMITTER: Vis DJ 

PROVIDER: S-EPMC11384948 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature